Association Study of rs3184504 C>T Polymorphism in Patients With Coronary Artery Disease.

Cardiovascular disease has become the main factor of death and birth defects in the world and also in Iran. New clinical studies have shown that early diagnosis of patients with coronary artery disease (CAD) can contribute to effective prevention or therapeutic structures, which reduce mortality or the next chance of cardiovascular events, and increase the quality of life. Most studies on CAD disease and its genetic risk factors so far, have been done excluding the Iranian population. PubMed was used to search for all relevant studies published on or before 2013 and rs3184504 was selected for association study for CAD. A total of 200 subjects with 100 cases and 100 controls were ultimately included in the analysis. Blood samples were collected and after DNA extraction the DNA analysis was performed by TaqMan Probe Real Time PCR to evaluate the association between candidate variant with the disease and some blood biochemical factors. Our study demonstrated that there was not a direct association between rs3184504 C>T variant with risk of CAD in Iranian population, whereas, there is a significant association between this variant with increased blood LDL and diastolic blood pressure. Further molecular analysis and other disease association studies are necessary in the Iranian population.

through the loss of endothelial function and integrity, after percutaneous revascularization and transplant arteriosclerosis (20)(21).
Endothelial cell (EC) migration is a mechanically integrated molecular process which involves dynamic and coordinated alteration in cell attachment and cytoskeleton organization (22)(23).
A series of steps are required in this process including cellular extension and formation of membrane protrusion, termed lamellipodia that push the leading front and lastly, cell contraction which allows forward progression. Attachment of protrusions to the extracellular matrix (ECM) is mediated by integrins that function as receptors for cell-adhesion molecules.
As mentioned, there are also genetic risk factors causing CVD. The new strategy of genomewide association (GWA) studies is starting to demonstrate novel genetic factors which contribute to disease risk. Many genetic variants that predispose to CVD spanning from common polymorphisms (minor allele frequency >1%) to rare, highly deleterious mutations responsible for Mendelian diseases which are usually identified by linkage studies, alone or in combination, modulate the risk of the disease. A different approach named genetic association analysis is used in order to identify the genes involved in complex diseases (24). In the case of complex diseases such as MI , linkage analysis is compounded by genetic heterogeneity of the disease and other factors such as incomplete penetrance of genes causing the disease and their interaction with environmental factors. In addition, the high prevalence of the disease-causing allele in the population, and late onset of disease can be named as another instance (25). Studies based on Meta-analysis technique published on 2011 demonstrate that specific genetic loci were introduced in association with CVD and more specifically with MI. Alteration in expression in some of them causes increasing risk of MI (25)(26). Recent GWAs studies show that different SNPs on 12q24 locus (such as rs3184504 on Lnk) are associated with platelet count, hemoglobin concentration, hematocrit and blood pressure (27).  (28). The named SNP, in addition to its companionship with eosinophil, cooperates with other increased blood parameters such as the total amount of platelets, leukocytes and red blood cells.
Regarding the platelets and leukocytes the cooperation was evaluated by CAD onset (28).
Genetic diversity can be related to the regulation of blood pressure fluctuation through structural change of encoded proteins and alteration in gene expression (quantity of proteins) (29).
Regarding the SH2B3 gene, based on existing studies, there is a significant correlation between the non-synonymous SNP rs3184504 and the Deficiency of Lnk may cause increased signaling by cytokine and thrombopoietin receptors such as c-kit and c-mpl that are essential and critical for growth of hematopoietic stem and progenitor cells (20,39). Another study performed in London confirmed association between increased LDL and rs3184504 C>T variant (40). The aim of this study was to investigate the association between CAD, increased LDL, blood pressure and rs3184504 C>T variant.

Patients and controls
A total of 200 genetically unrelated Iranian subjects, comprising 100 individuals with MI and 100 normal controls from Tehran, Babol, and Mashhad cities were enrolled in the present study.
All cases were selected based on the World Health Organization (WHO) criteria as described (41).
Inclusion criteria: male and female, age over

Discussion
Many studies on CAD disease and its genetic European and 5000 Asians which revealed that rs3184504 had association with the number of eosinophils in blood (27). Eosinophils are